Required Application Instructions
It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.
I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information
This Funding Opportunity Announcement (FOA) is soliciting applications to support existing cohorts to address how pre-, peri-, and post-natal environmental exposures impact childhood development and health outcomes as part of the Environmental influences on Child Health Outcomes (ECHO) program. Increasing evidence suggests that exposures early in life (e.g., social environment, maternal behavior, nicotine, diet, microbiome) can result in health deficits and lead to life-long consequences. The purpose of this FOA is to leverage and build upon existing cohort infrastructure to prospectively investigate the role of early life exposures and underlying biological mechanisms in childhood health and disease. This will advance our understanding of how the in utero and early post-natal environments impact childhood outcomes and influence the child's predisposition for health, resilience, and disease. The ultimate goal is to identify critical periods of development that are impacted by multi-level exposures, and identify opportunities to mitigate risk of disease and maximize health.
This FOA runs in parallel with companion FOAs that solicit applications for the Coordinating Center (RFA-OD-16-006), Data Analysis Center (RFA-OD-16-005), Patient/Person Reported Outcomes Core (RFA-OD-16-003), Administrative Supplements to the Children's Health Exposure Analysis Resource (CHEAR) (PA-16-046), and IDeA States Pediatric Clinical Trials Network (RFA-OD-16-002 and RFA-OD-16-001), and a Genetics Core to be released in FY17.
Funding for an exploratory UG3 stage will be used for planning, feasibility testing, and developing study documents, including the study protocol and Manual of Procedures. UG3 projects that have met milestones will be administratively considered for transition to the UH3 implementation phase. Applicants responding to this FOA must address objectives for both the UG3 and UH3 phases.
Applicants are encouraged to pre-assemble more than one cohort in their applications.
NIH is establishing the new Environmental influences on Child Health Outcomes (ECHO) program to address the longitudinal impact of pre-natal, peri-natal, and post-natal environmental exposures on pediatric development and health outcomes with high public health impact. To do so, NIH will support multiple synergistic, longitudinal studies using extant cohorts that represent various environmental exposures (e.g., physical, chemical, biological, behavioral, social). All longitudinal studies will share standardized prospective data collection to address research questions that focus on four key pediatric outcomes. The program will be overseen by a NIH Program Director, a Steering Committee, and an External Scientific Board. ECHO is being solicited through 7 FOAs, including this FOA that is focused on leveraging of existing cohorts to study early life exposures in children's health and disease.
ECHO is focused on key outcomes associated with early life exposures. For the purposes of this initiative, early life is defined as the period from preconception, fetal life, birth, and up to age 5 years old. There is no restriction on the current age range of cohort members, but all applicants must show that the proposed cohort already has early life exposure data and/or can collect high-quality data on early life exposure(s) among cohort participants. The scientific merit of the early life exposure data proposed and the value that a cohort would bring to the ECHO Consortium will be evaluated in peer review.
Successful prevention strategies of childhood disease require a clear definition of incident cases and differentiation from pre-clinical stages of disease. Longitudinal collection of multiple types of data (clinical, diagnostic, and molecular) can inform the trajectory of disease processes and/or age-related changes. Leveraging and combining rich extant datasets from multiple longitudinal cohorts provide a unique opportunity to enhance research in environmental origins of disease, by increasing the power of observations that goes beyond one cohort, one exposure, and one disease. Combining cohorts will help us to efficiently define and understand typical growth and development in children by:
This and the companion FOAs will form a consortium of investigators to evaluate the effects of early life environmental exposures (including in-utero exposures) on child development and health outcomes through investigation of existing data, exposure analysis of existing and/or prospectively-collected biospecimens, and collaborative standardization of prospective data collection from ECHO's multiple extant cohorts. Combining larger pre- and post-natal cohorts with more selective, high-risk (e.g. of asthma, obesity) pre-, peri- and/or post-natal cohorts will permit the development of a large dataset that can serve as a base cohort for studying typical development and questions related to population-based risk and also serve as a way to examine potential risk factors for diseases/disorders of childhood.
In response to this FOA, investigators with relevant cohorts should propose hypotheses about the impact of early life exposures on child development, health, and disease outcomes during childhood.
Characteristics of cohorts may include, but are not limited to:
As investigators in ECHO, cohort leaders will interact with the Coordinating Center (CC), Data Analysis Center (DAC), and Children's Health Exposure Analysis Resource (CHEAR), Genetics, Patient/Person Reported Outcomes (PROs) Cores to design a multi-cohort protocol to answer scientific questions of how early life exposures influence childhood health for each of the focus areas. This collaborative protocol will be implemented across all ECHO focus-area cohorts and include standardized procedures for prospective collection of the following Core Elements listed below.
Cohort applicants should include data collection plans for at least one of the four key development and health outcome Focus Areas, while addressing how future data and biospecimen collection might inform the other areas:
1) Upper and/or lower airway (e.g. asthma, allergies, sleep-disordered breathing)
2) Obesity (e.g. nutrition, metabolic risk factors, activity level)
3) Pre-, peri, and post-natal outcomes (e.g. birth defects, prematurity, neonatal/infant mortality)
4) Neurodevelopment (e.g. attention, cognition, emotion, social/language/behavioral development)
In the UG3 phase, applicants should leverage retrospective and newly collected prospective data from longitudinal cohorts that have existing maternal-fetal-, perinatal-, and/or early postnatal-relevant clinical data and biospecimens for exposures analyses of relevance to at least one of the four Focus Areas (listed above). In the UH3 phase, cohorts will participate in standardized prospective data collection across all cohorts, with a focus on integrating the retrospective and prospective data and integrating analyses across cohorts. Applicants are encouraged, but not required, to pre-assemble more than one existing cohort prior to submission and are strongly encouraged to work with biostatisticians when developing a research plan. Basic mechanistic studies that can only be done using samples from the human cohort(s) are encouraged in both UG3 and UH3 phases.
The initial UG3 phase should support:
The UH3 phase of the application should focus on how the applicant could add to the ECHO consortium, and in what ways the ECHO consortium (with anticipated > or = 50,000 subjects) could examine the influence of multi-level environmental exposures on childhood health outcomes, using both retrospective data and prospective data. Of particular interest would be applications that explore the human biological mechanisms for links between early life factors (e.g. social/behavioral and physical) and childhood health data. Collaboration with a biostatistician is highly encouraged.
The UH3 phase should support:
Descriptions of Core Elements for Prospective Data Collection
All applicants should anticipate collecting Core elements in the prospective phase of ECHO funding support. Specific assays and measures will be delineated and standardized according to a multi-center protocol developed by the ECHO Steering Committee. This will be a collaborative effort between the PDs/PIs of the cohorts, the CC, DAC, COREs, and NIH Program Staff. If already present in cohorts upon inclusion into ECHO, the Core Elements will be harmonized across studies, as well.
Core Elements include:
To assist in the collection and analysis of these common data elements, the ECHO consortium will support centralized capabilities including a system for Patient/person Reported Outcomes, genotyping and analysis, and assessment of environmental factors in biospecimens. Collecting biospecimens suitable for studies of the microbiome and epigenetics also will be encouraged where appropriate.
This FOA will support the collection of demographic information beyond basic information for parents and children (e.g. age, race/ethnicity, gender, socioeconomic status). Additional demographic information are encouraged, particularly those that are important to evaluate environmental exposures (e.g. geographic residential and/or daycare/school locations) and may be expanded for multi-cohort protocols once determined by the Steering Committee.
Typical Early Development
All children should be assessed on basic developmental, age-appropriate physical, cognitive, and social and emotional milestones, such as those recommended by the American Academy of Pediatrics. These assessments could be obtained through electronic health records (EHR), through observations that are included in the study, or via parent reports. An optional sub element is the microbiome.
Genetics is a key component for fully understanding mechanisms underlying environmental exposures and the typical and atypical child development. Ideally, cohorts would already have biospecimens (e.g. buccal swabs, saliva, blood) from which DNA could be extracted and genotyped through participation in the ECHO consortium. If biospecimens are not available, appropriate consent for use, or existing biospecimens prove to be inadequate for genotyping, cohorts should anticipate collecting and genotyping such biospecimens as a part of the prospective ECHO data collection effort. At a minimum, ECHO plans to genotype the children in the cohort. If DNA samples are available through funded cohort studies, parent-child trios (or parents and children) may be genotyped. An optional sub-element is epigenetics.
Environmental exposures can comprise a broad range of assessments, including those for chemical and non-chemical stressors. Applicants are strongly encouraged to include measures of both behavioral/social and physical environments. The goals of including multilevel environmental assessments include, but are not limited to:
Examples of key behavioral/social environments include, but are not limited to:
Parents and/or children: smoking status, substance abuse, physical activity and diet, stress, depression, and other mental health conditions, education, overall Health Related Quality of Life, perceived family and peer support, parent-child relationships.
Examples of key chemical and non-chemical stressors include, but are not limited to:
Chemical stressors may be considered as single chemicals, or as mixtures and aggregates as may be found in consumer products used by children and environments frequented by children.
Non-chemical stressors include modifying factors such as diet and nutrition, physical activity including time spent in various microenvironments, psychosocial and socioeconomic factors, and the design of the built environment (e.g. settings: home, school, play areas) from birth through young adulthood.
The Children's Health Exposure Analysis Resource (CHEAR) http://www.niehs.nih.gov/research/supported/dert/programs/chear/ Core will provide laboratory and statistical analyses to add or expand the inclusion of environmental exposures in Pediatric Cohort research. The CHEAR Core (or similar resource) is strongly encouraged to provide
1) rigorous assessment of a range of environmental exposures, xenobiotics, physiological measurements, and other biological indicators of environmental exposure and response in biospecimens including typically collected biofluids (blood, serum, plasma, urine) as well as other biospecimens including hair, placenta, and deciduous teeth, and (2) statistical tools and data science approaches to manage and analyze all of these newly generated datasets in a cohesive and integrated manner. CHEAR and the ECHO CHEAR Core will enable the children's health research community, including ECHO investigators, to enhance and build on their existing studies by expanding the capability or capacity of measuring both chemical and non-chemical stressors that effect children's wellbeing and development. It is expected that by implementing standard measures and analyses across studies and encouraging collaborations and networking, the CHEAR Core will enable meta-analyses and integration of datasets of multiple cohorts and other study designs.
The output of these UG3/UH3 projects, to be facilitated by a CC (RFA-OD-16-006) and a DAC (RFA-OD-16-005), will be a collaborative group of extant pre- and peri- and post-natal cohorts that address the Core Elements, are prepared to address research questions related to the Focus Areas, but are also staged to work together to collect harmonized and standardized data focused on understanding pre-, peri- and post-natal environmental influences on child health and development.
Applicants should propose hypotheses on how early life environmental exposures affect child heath (including growth/development, clinical outcomes, and genetics) during the proposed prospective follow-up of the extant cohort.
Applicants should propose research relevant to one or more of the Focus Areas described above. Applicants should propose a single study design leveraging existing exposure data and /or biospecimens and additional prospective data collection of the cohort on focus area health outcome(s) and/or genetics to address a specific hypothesis of the role of environmental exposures on pediatric health outcomes. Patient reported outcomes are encouraged for key focus area applications. In addition, the Steering Committee will collaboratively identify PROs essential for collection across all cohorts. Applicants are encouraged to utilize PROMIS measures [see NIH-funded Patient-Reported Outcomes measures and functional assessments ("NIH Toolbox") at www.healthmeasures.net and NIH PhenX Toolkit: https://www.phenx.org/]
Assessment of environmental exposures is required, either via internal assessments (e.g. biological assays that quantify exposure levels in the body) or via external assessments (e.g. assays that quantify environmental exposure levels through mobile devices, geocoding, questionnaires). Environmental exposures include, but are not limited to, chemical exposures, biological (e.g. microbial/antigenic), social, behavioral, climate, built and physical environment. Applicants are strongly encouraged to leverage FY2015 resources CHEAR and PRISMs (
http://www.nibib.nih.gov/funding/funding-opportunities/prisms ).The applicant should describe in the research plan when and what clinical data, biospecimens, and resources will be collected and analyzed during the longitudinal follow-up of the cohort.
All cohorts funded as part of ECHO must agree to participate in prospective data collection efforts and are expected to reserve a portion of their budget for these efforts. These prospective data collection efforts will be related to the Core Elements and Focus Areas, and will be developed and agreed upon by a Steering Committee comprising PDs/PIs of the CC, DAC, PRO Core, CHEAR Core, the Genetics Core, the IDeA States Pediatric Clinical Trials Network DCOC, and each of the Cohort sites, as well as the NIH ECHO Program Director and NIH Project Team during the first year of the awards. The DAC, along with assistance from the CC, will be charged with coordinating and implementing the data collection process (including informed consents, protocols, case report forms, MOPs after funding). All cohorts will be expected to participate in an initial startup meeting and other meetings among all cohorts, including Focus Area and Project Coordinator subcommittees of the SC. These meetings will focus on tasks related to harmonizing the cohorts and selection of prospective measurement.
Criteria for Transition
Performance metrics will be evaluated before the UG3 award is transitioned to the UH3 phase after the second year of funding. Final milestones will be designed during the first year of the UG3 planning phase. The application should specify the milestones for transition, which will be evaluated during peer review and used as the basis of programmatic review at the transition time.
It is suggested that applicants consider the demonstration of the following when developing milestones for the application:
Other programmatic criteria that would affect the transition from the UG3 phase to UH3 phase include contributions to the larger goals of ECHO, the availability of NIH funds, NIH program priorities, and NIH leadership approval.
Selected Research Examples:
Research examples include, but are not limited to:
This FOA is intended to support only human studies. Applications that include animal studies will not be considered responsive. Patient registries alone, without a hypothesis to be tested, will not be responsive. Conduct of a new clinical trial is not the intent of this FOA, but an existing clinical trial cohort may be used if appropriate.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
Non-domestic (non-U.S.) Entities (Foreign Institutions) are
eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.
Program Directors/Principal Investigators (PD(s)/PI(s))
All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.
Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.
For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.
PD(s)/PI(s) should possess a doctoral degree in a relevant field such as maternal and fetal medicine, neonatology, pediatrics, key focus area expertise, and is/are required to commit no less than 2.4 person-months (20 percent) combined effort to the ECHO Extant Cohort program. PDs/PIs must have clinical research and/or epidemiology expertise. Active participation of the PDs/PIs is expected during all phases of the ECHO clinical research study.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Applicant organizations may submit more than one application, provided that each application is scientifically distinct.
The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:
Applicants must obtain the SF424 (R&R) application package associated with this funding opportunity using the "Apply for Grant Electronically" button in this FOA or following the directions provided at Grants.gov.
It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.
For information on Application Submission and Receipt, visit Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.
Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.
By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:
The letter of intent should be sent to:
Erica L. Spotts, Ph.D.
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed, with the following exception: For this specific FOA, the Research Strategy section is limited to 30 pages.
The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
Facilities & Other Resources: Describe the infrastructure available from the parent study.
All instructions in the SF424 (R&R) Application Guide must be followed.
One individual must be designated as an alternate PD/PI who is able to serve in the absence of the PD/PI. Multi-disciplinary teams are strongly encouraged with clinical research expertise in child development and/or health outcomes, epidemiology, exposure assessments. Personnel with expertise in data management of the extant cohort should be included if available. Key personnel should include Biostatistics expertise. Collaboration with a biostatistician is highly encouraged.
All instructions in the SF424 (R&R) Application Guide must be followed.
Applications should budget for the following:
Multicenter Data Collection
Budgets must include no more than $1,200 total costs/subject/year for Key Focus Area specific clinical data and exposure assessments (non-overlapping with existing funding).
Budgets must include no more than $1,000 total costs/subject/year for ECHO-Core elements data and sample collection and transfer to the CC and Cores. Data collection and transfer to the CC for the multicenter protocol requirements (if awarded in future years) will be restricted and may be renegotiated based on performance, and will not be re-budgeted without NIH prior approval.
The budget for the first year, which includes a 9-month planning phase, should include a minimum of 2.4 calendar months effort for the applicant PD/PI or a minimum of 2.4 calendar months combined effort for all PD(s)PI(s) if the multiple PD/PI strategy is used, clinical study coordinator, extant cohort Coordinating Center Data Management PI and/or Project Manager, travel funds for four 2-day Steering Committee meetings in Bethesda, MD, for the PD/PI and coordinator, travel funds for 2-3 days of coordinator training, and additional items as needed.
There will be two types of costs that applicants need to consider: 1) resources provided for the existing cohort's own research, and 2) costs related to the Common Elements that will be collected for all participants in the consortium. The per enrolled/active participant, per year allowable cost for costs related to the Common Element data collection is up to $1000 in total costs.
For FY17-22 all costs required for the proposed research must be included in the application and be fully justified. The budget must include support for clinical study coordinators at sites where prospective follow up will be conducted; a minimum of 2.4 calendar months effort for the applicant PI or a minimum of 2.4 calendar months combined effort for all PDs/PIs if the multiple PD/PI strategy is used. The budget should include the costs associated with identification, screening, and recruitment of subjects and, if indicated, new subjects; the costs of obtaining, processing, and storage of biological specimens; and the costs associated with the analyses required for the physiologic and/or molecular/biologic aims of the research. Travel costs for four Steering Committee meetings per year in Bethesda should be included for several members of the Research Center. If CTSA resources are to be used, and a fee is charged, please note this in the budget.
The elements of patient-related research costs should be clearly identified, and included both as a per-subject amount, and a total amount. Subject-related funds can be moved by NIH after award from one site to another to adjust for variability in recruitment or other needs that might arise. Indirect costs (facilities and administration) are not permitted to be included in patient-related research costs. In addition, IRB fees are not permitted to be paid from direct costs in NIH grants. They are considered to be indirect costs.
For multicenter concept applications, the budget must include the costs associated with coordination of biospecimen collection from all patients to be recruited, not just the number of patients that are expected from the applicant site. Costs may include those associated with shipping specimens, images, or other material; staff time to develop operational and training manuals, analyze data, specimens, or images and report the results; any storage capability required at the sites; travel for four Steering Committee meeting per year in Bethesda, MD; and other components as required.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Applicants should propose and test new hypotheses (not already funded in the extant cohort) that explore child development and/or health response in one or more Focus Areas to various exposures by leveraging existing cohort data and biospecimens that can be completed in the UG3 phase (the secondary analyses) as well as the UH3 phase (the prospective data analyses). Applications proposing basic mechanistic studies should describe the utilization of samples from the human cohort(s). In addition to the standard background, significance, innovation, and approach that must be discussed in the Research Strategy, applicants should describe the population characteristics, data, and biospecimens available from the parent study and propose how any additional normal or at-risk participants, new data, and biospecimens to be collected will add to the ability to examine trajectories of health, risk, resilience, and disease. Applicants should propose how increasing sample size(s) through pooling data via the ECHO consortium could be leveraged to answer collaborative research questions on the impact of the environment on child health in the focus area of expertise.
The description of the planning period should include activities required to ensure that recruitment can begin by the end of FY16, such as finalizing protocols, obtaining pilot data if needed, obtaining IRB approval, establishing research collaborations with other sites, completing coordinator training, testing the feasibility/usability of existing biospecimens, assessing feasibility of recontact and/or reconsent, and ordering necessary supplies.
Applicants should detail what data and biospecimens they have available, over what period of time, for what ages, etc. Data relevant to the proposed research should be included in the body of the application. To be included are estimates of the number of participants for prospective follow-up, based on existing retention and potential attrition rates, and a timeline for enrollment and planned cohort-specific data collection.
All applications should provide a strategy to contact/recontact participants for enrollment in the longitudinal follow-up (including appropriate consent). This is particularly important in cases where the investigators are proposing to restart a closed study. In such instances, investigators are required to provide pilot data on the ability to recontact and enroll a sufficient portion of the participants, demonstrate that they could collect basic milestone data (e.g. height, weight, basic medical information) in the first funded year of the study, and provide a compelling argument for why restarting this study is critical for the overall data consortium effort. Applicants should provide a plan for expected data collection beginning in the first year of the funded study and minimum targets (milestones) to be achieved to qualify for second phase funding.
The research strategy for FY17-22 (the prospective phase of longitudinal data collection) should include a description of the clinical study design, including hypotheses, study objectives, target population, total number of subjects required at the site (for the research project) and across the ECHO Program (for the multicenter concept), anticipated duration of recruitment and data analysis, and a description of the statistical analysis plan. The Research Strategy should describe the patient population and recruitment resources including experience with recruitment and retention of children available at the Research Center site that would benefit the Program (e.g. CTSA, Maternal Fetal Medicine Unit, and/or Neonatal/Pediatric resources). The Research Strategy should propose specific milestones that will be used to evaluate success of the project throughout the duration of funding and particularly for evaluating the transition from UG3 to UH3 funding.
The research strategy should also detail how the specific cohort is important for the entire synthetic cohort effort and should include a proposal for simple validated data collection of incident disease outcome in one focus area that can be implemented across all cohorts (e.g. validated survey instrument for detection of incident asthma).
Applicants should propose how increasing sample size(s) through pooling clinical and environmental exposure data via the ECHO consortium could be leveraged to answer multi-cohort collaborative research questions on the impact of the environment on child health in the focus area of expertise and could easily be applied across all ECHO cohorts with anticipated subject population of ~50,000 children of various ages. This should include a strategy for prospective collection of environmental exposure measures relevant for ECHO multi-cohort protocol and health outcome measures.
The applicant institution and PD(s)/PI(s) should document clinical and research collaborative experience of the group as a whole in recruitment, and retention (at least 80%) of maternal/fetal, infant, and/or pediatric study participants in the extant cohort. Detailed data on the population available for each proposed study (retrospective and prospective single and multicenter) should be included. Clearly describe the formal organizational structure of the Research Group, including lines of authority and responsibility, with particular attention to the relationship of the organizational structure to ECHO's major objectives.
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:
Resources generated by the ECHO Program are also expected to be widely shared with the Consortium and the broader scientific community for research. The Steering Committee will develop and implement Consortium-wide approaches for resource deposition and use, including submission to national repositories as appropriate. Resources include human biospecimens, instrumentation and assays, special standards, protocols, and bioinformatics tools.
Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.
When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.
Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.
See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov
Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH's electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.
The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization's profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.
See more tips for avoiding common errors.
Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.
Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.
Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.
Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).
Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.
Does the project address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? Is there a unique contribution of the existing cohort to the anticipated multi-cohort protocol of ~50,000 pediatric subjects? If not unique, what is the value of the cohort to the goals of ECHO (i.e. to leverage and build upon existing cohort infrastructure to investigate the role of early life exposures and underlying biological mechanisms in childhood health and disease; to identify critical periods of development that are impacted by multi-level exposures, and identify opportunities to mitigate risk of disease and maximize health)? If new data/specimen collection is proposed, is the value for examining trajectories of risk, resilience, and disease advanced? What is the likelihood that that concept could (or would) be applied across ECHO cohorts?
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? Does the PD/PI(s) have adequate expertise in and a documented history of contributions to the field of environmental exposures and child health outcomes? Does the PD/PI have prior experience with collaborative research? Does the PD/PI have prior experience with successful timely recruitment and retention of pediatric subjects? Will the investigators bring valuable areas of expertise to the ECHO program that will maximize flexibility for the program?
Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?
If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed? Are the UG3 milestones reasonable and appropriate? Does the research plan detail how the specific cohort would be important for the entire synthetic ECHO cohort effort and include a proposal for simple validated data collection of incident disease outcome in one focus area that could be implemented across all cohorts? Is there evidence of sufficient clinical data and biospecimen management, completeness, and quality to suggest significant contributions to the ECHO multi-cohort goals? Are the environmental exposures for targeted and untargeted analyses appropriate? Does the application specify milestones that adequately assess progress during the UG3 stage that would permit transition to the UH3 phase? If met, do these milestones provide adequate information to program staff to decide on funding the UH3 phase?
Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements? Is there evidence that the institution has a track record in supporting collaborative clinical investigations? Are there institutional resources that will be leveraged (CTSAs, networks, Cores)?
As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.
For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.
For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.
When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.
As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.
Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.
Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).
For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.
Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.
Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by CSR, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.
As part of the scientific peer review, all applications:
Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.
Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the appropriate national Advisory Council or Board. The following will be considered in making funding decisions:
After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.
Information regarding the disposition of applications is available in the NIH Grants Policy Statement.
If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.
A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee's business official.
Awardees must comply with any funding restrictions described in Section IV.6. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.
Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.
All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.
Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person's race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator's scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.
For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.
Cooperative Agreement Terms and Conditions of Award
The following special terms of award are in addition to, and
not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB)
administrative guidelines, U.S. Department of Health and Human Services (DHHS)
grant administration regulations at 45 CFR Part 75, and other DHHS, PHS, and
NIH grant administration policies.
The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.
The PD(s)/PI(s) will have the primary responsibility for:
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
NIH assistance to the ECHO operations will be provided by the ECHO Program Director and the NIH ECHO Team, as well as by NIH Project Scientists or other NIH staff that may be assigned to across-ECHO studies or studies within one of the four ECHO scientific focus areas. NIH staff will have substantial scientific/programmatic involvement during the conduct of this activity through technical assistance, advice and coordination above and beyond the normal program stewardship role for grants. It is anticipated that decisions regarding the Pediatric Cohort activities will be reached by consensus and that the NIH staff members will participate in this process. In various matters related to study approval and oversight, the NIH staff will have final decision authority, as described below.
Areas of Joint Responsibility include:
ECHO Steering Committee
External Scientific Board
Data and Safety Monitoring Board
Development of Milestones
Any disagreements that may arise in scientific or programmatic matters (within the scope of the ECHO awards) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. The panel members will be a designee of the ECHO Steering Committee, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.
A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.
We encourage inquiries concerning this funding opportunity
and welcome the opportunity to answer questions from potential applicants.
eRA Service Desk (Questions regarding ASSIST, eRA Commons
registration, submitting and tracking an application, documenting system
problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Customer Support (Questions
regarding Grants.gov registration and submission, downloading forms and
Contact CenterTelephone: 800-518-4726
(Questions regarding application instructions and process, finding NIH grant
Email: GrantsInfo@nih.gov (preferred method of contact)
Erica L. Spotts, Ph.D.
Office of Behavioral and Social Sciences Research (OBSSR)
Carol J. Blaisdell, M.D.
National Heart, Lung, and Blood Institute (NHLBI)
Tara A. Schwetz, PhD
Office of the Director (OD)
Valerie Durrant, Ph.D.
Center for Scientific Research
Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.
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